Why Should FDA Regulate Drugs?

An Interview with Janet Woodcock, M.D.,
Director of FDA's Center for Drug Evaluation and Research

Is the Food and Drug Administration in need of reform? Some critics of the agency, in Congress and outside, argue that the agency should be overhauled to make it work more efficiently. FDA supporters disagree, pointing to record-setting drug approvals and other agency accomplishments in recent years.

FDA's Center for Drug Evaluation and Research (CDER) is the part of the agency that regulates all drugs marketed in the United States: brand-name and generic, prescription and over-the-counter.

Since June 1994, the center has been directed by Janet Woodcock, M.D., a rheumatologist who worked in FDA's Center for Biologics Evaluation and Research for eight years before becoming CDER's director.

Despite her center's record 131 drug approvals in 1996, including new treatments for AIDS, Alzheimer's disease, and diabetes, and despite a much-reduced median review time of about 15 months in that year, some continue to question the agency's role in the drug review and approval process. And you, as a consumer, may wonder, "Why should a government agency even be involved in my decisions about the drugs I want to take?"

In the following interview, Woodcock gives her views on these issues.

Q. Why not trust consumers to decide for themselves which medicines work for them?

A. I don't think it's in the government's best interest to stand between people, especially those who are desperately ill, and their desire to take medicine. But that libertarian issue shouldn't be confused with the scientific issue of whether patients can tell what medicines work, because with almost any drug treatment we use today, they can't tell.

Doctors thought for years they could tell what worked. In the 1960s, for example, doctors were convinced that diethylstilbestrol, or DES, was terrific for preventing early miscarriages, and they gave it to thousands of women in pregnancy. "The women had miscarriages before, and I put them on this DES, and some of them didn't have miscarriages. So obviously, it's very effective," doctors thought.

In fact, when DES was actually subjected to scientific testing, it had no effect on miscarriage whatsoever. Not only was it absolutely ineffective, but unfortunately it had delayed negative health effects on the fetus.

We had a more recent experience like this with a heart rhythm drug. After people have heart attacks, they can have extra beats. And it's known that a percentage of people with those extra beats will have sudden death. Well, drugs were discovered that made the sudden beats go away, and people thought, "Wonderful! Make the beats go away, and sudden death will go away." The medicine became the standard of practice throughout the United States; everybody was using the drug.

There were some skeptics at the National Institutes of Health and FDA that said the drug ought to be tested. NIH set up a trial, and what they discovered shocked everyone: Yeah, the drugs make the beats go away, but the people who were put on the drugs had sudden death at a substantially higher rate than the people who were just left having the beats. The drugs actually made the problem worse, and maybe more probable.

Even the people who did the trial were later haunted by the fact that they had given some people that drug. They were people the researchers knew, and some of them died.

So the answer is, many, many very smart people have thought they knew what drugs would help them and what drugs would hurt them, and clinical tests again and again have proven them wrong. They didn't know.

Q. What is there to lose by giving people with life-threatening diseases
like AIDS and terminal cancer access to whatever drugs they want?

A. If we didn't test drugs--if people could take whatever they wanted without any testing--there would be no way to tell whether any of the thousands, millions, of candidate drugs out there worked. So no one would ultimately benefit.

For people with life-threatening illnesses, even the patient groups don't agree on where the right balance is between identifying treatments that will really improve patients' health and allowing people to have immediate access to experiment with drugs that might work for them.

I think AIDS is a good example. We had a lot of discussions with the AIDS activists early on about access to treatments. And FDA put together many programs to allow people early access to those drugs even before they were approved.

But at the same time, companies did pursue testing to see if these agents worked. Ultimately, some drugs were dropped, because they didn't work or because they were so toxic that the risks outweighed the benefits. And good drugs were found and then approved by FDA.

Now we're decreasing mortality with HIV. So every person with HIV has a path they know they can take of drugs that will work to improve their health, and have been proven to do so. If we'd gone down the other path, and everyone had been able to try anything they wanted with no testing, then we'd still be at the same point so much later into the epidemic: Everyone would have total availability to all drugs, but we wouldn't know what worked.

Now some of the AIDS activists are actually telling us they want more rigorous testing because, as they study their disease and the treatments, they realize they need information to make choices about which drugs they should take, even among the approved drugs. They want FDA to mandate more big trials that would include combination therapy. "What if I start this combination early, versus if I take this single drug first? Which would help me to be in better health 10 years from now?" Those are the kinds of questions they want answered, and you can't answer those questions unless you do scientific testing.

Q. Isn't FDA infringing on drug marketers' freedom of speech
when the agency restricts what is said in drug labeling and advertising?

A. There is a category of speech called commercial speech when you're making a sales pitch. So, while some other kinds of speech are less restricted, things that are promotional in nature may have certain constraints legitimately put on them by FDA.

For example, drug labeling and advertising must be balanced and not misleading. In my opinion, consumers want truthful information; they want a lot of information, not hype.

Because people would like to receive all the latest information on a drug from the manufacturer, there has been a lot of debate about uses that are considered "off-label"--not approved by FDA.

Obviously, medical science doesn't happen in spurts, but continuously. After a drug is out on the market, health professionals continuously experiment with new uses. FDA thinks that's appropriate and doesn't want to restrict that kind of use of drugs. But we don't currently permit manufacturers to promote these new uses until it's proven that they work and are safe.

To help the situation, we've put out a draft guidance on how much information a manufacturer needs to get a new use put on the label. We think that will help to some extent.

Last year, the center approved 118 new uses for drugs that were already approved, way up from a few years ago. We think that manufacturers are motivated to send in applications for new uses because they know that the agency has been approving them promptly if they work.

Q. Could reforming FDA make it more efficient and save American tax dollars?

A. I think the center's efficiency has come far, but we still have improvements to make. When we talk about legislation to reform the agency, the first thing that must be done is to identify what problem exists. What problem are you trying to fix?

There has been a lot of rhetoric about FDA reform that hasn't been related to identified problems. Some people are saying the problem is that we're too slow. That clearly isn't the problem. During my three years as director of the center, some important changes have been made to make the center's work proceed faster and more effectively.

We are making as many processes as possible computer-based. But one of the biggest changes is the ever-improving review times for new drugs under the user fee program.

The idea behind user fees is that the industry is getting a service from the government in having their applications for marketing reviewed. And they should contribute directly to that. So five years ago, Congress, the industry, and FDA negotiated this user fee program. Industry would pay fees to add to FDA's resources for reviewing new drug applications. In exchange, FDA made a commitment to meet certain goals for review times.

CDER has been meeting all those goals. In fact, we've exceeded almost all the goals, and we expect to continue to exceed them. Basically, we've doubled the number of new drugs we're approving, and we've halved the review times.

One of the unique things about the user fee program, though, is that Congress only authorized it for five years, which expires at the end of September. So all the stakeholders--Congress, industry, the public--have to decide whether or not they're satisfied enough with the results to continue the program. Most of the interested parties I have talked to support the continuation of the user fee program.

In generic drugs, the workload has also gone up in the last couple of years. We're maintaining our review times--we've had difficulty shortening them on the generic drug side--but the generics staff has started some streamlining strategies over the last year to try to deal with the increased workload. They're working more closely with manufacturers--by faxing them information, communicating more by telephone, and meeting with them if necessary--to try to minimize the back-and-forth when an application has shortcomings.

So we still have work to do, but if you look at speed of introducing new medicines, we're the fastest agency among all the countries in the world with a formal regulatory system.

It takes a long time to change perceptions, though. For years, we were behind other countries in approvals, and there was what is called a "drug lag." In many cases, it took us years longer to review drugs than certain other countries. And that remains in people's minds.

But review time is only one facet of an effective center. People are now bringing up drug development times: the time it takes from a chemical's discovery in the laboratory, to its testing in animals, to its testing in people, to its review by FDA, which is necessary before marketing. People are saying that the drug development time is too long, and that maybe FDA has a part in that.

I think there are some things FDA can do to shorten the drug development times. What FDA does in drug development is to set certain standards. Clearly, if we did away with all the laws we have now, drug development time could be very short. A person could make a chemical, say, in their basement, and then they could put it on sale. That's going too far.

What we can do is evaluate our standards to make sure that all the information we require is absolutely necessary, and there are no extras. And we must be very clear about what information is required at each stage of drug development. The clearer we are, and the more the standards are universal, the easier drug development will be.

About a year ago, we streamlined what's called the IND process. That is, we provided some guidance on the minimum amount of animal chemistry information necessary to start the drug development milestone of testing in humans.

Also, over the last few years, FDA, Japan, and the European Union have been negotiating to standardize technical requirements under the International Conference on Harmonization (ICH). Then, companies won't have to repeat things unnecessarily.

What the harmonization among countries means is that data that a drug company collected to submit to, say, Japanese authorities will be the same or similar data as that required for FDA. It means reducing the amount of testing, but each country would still make its own decision about whether to approve a drug.

So far under the ICH, major progress has been made toward standardizing the information that is filed about side effects to help us detect unexpected side effects earlier, and standardizing the kinds of safety testing in humans that is required.

But to say FDA alone should decrease development times would be a big stretch. Because pharmaceutical companies develop the drugs, not FDA, much of the burden for shortening development times and decreasing development costs lies with them.

I think manufacturers are very interested in shortening drug development times. We know it can be done. For example, with the AIDS drugs, where people put in a full-court press on developing drugs, they were developed very rapidly, from the test tube to the clinic to marketing.

CDER's mission involves not only assuring that safe and effective drugs are available to the public, but that unsafe or ineffective drugs are kept off the market.

It's an interesting balance, and even consumer groups disagree about what the right balance is. Some groups are very risk-averse, and they don't believe FDA should approve any drug that has harmful effects. Well, most drugs have harmful effects, and you have to make sure that the drug's benefits outweigh its harmful effects.

We at CDER think we've achieved the proper balance, given all the different parties and their different interests. While there will never be complete agreement, most people seem to agree on one thing: FDA should keep drugs off the market that ultimately will harm or kill people and have to be withdrawn.

Tamar Nordenberg is a staff writer for FDA Consumer.

FDA Consumer magazine (September-October 1997)